The Encyclopedia of Natural Medicine, 3rd Ed.

Anemia

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• Pallor, weakness, and a tendency to become fatigued easily

• Low volume of blood, low level of total red blood cells, or abnormal size or shape of red blood cells

Anemia is a condition in which the blood is deficient in red blood cells or the hemoglobin (iron-containing) portion of red blood cells. The primary function of the red blood cell (RBC) is to transport oxygen from the lungs to the tissues of the body and then bring carbon dioxide from the tissues to the lungs, where it is exhaled. The symptoms of anemia, such as extreme fatigue, reflect a lack of oxygen being delivered to tissues and a buildup of carbon dioxide.

There are three major classifications of anemia.

1. Anemia due to excessive blood loss

2. Anemia due to excessive red blood cell destruction

3. Anemia due to deficient red blood cell or hemoglobin production

Anemia Due to Excessive Blood Loss

Anemia can be produced during acute (rapid) or chronic (slow but constant) blood loss. Acute blood loss can be fatal if more than one-third of total blood volume is lost (roughly 1.5 l). Since acute blood loss is usually quite apparent, there is little difficulty in diagnosis. Often blood transfusion is required.

Chronic blood loss from a slow-bleeding peptic ulcer, hemorrhoids, or menstruation can also produce anemia. This highlights the importance of identifying the cause through a complete diagnostic workup by a qualified health care professional.

Anemia Due to Excessive Red Blood Cell Destruction

Old red blood cells, as well as abnormal RBCs, are removed from the circulation primarily by the spleen. If destruction of old or abnormal RBCs exceeds the body’s ability to manufacture new RBCs, anemia can result. The most common cause of excessive destruction of RBCs is abnormal RBC shape.

A number of things can lead to abnormal RBC shape, including synthesis of defective hemoglobin, as seen in hereditary conditions such as sickle-cell anemia; mechanical injury due to trauma or turbulence within arteries; hereditary RBC enzyme defects; and vitamin or mineral deficiency.

Anemia Due to Deficient Red Blood Cell or Hemoglobin Production

Insufficient production of RBCs or hemoglobin is the most common category of anemia, and by far the most common cause is nutritional deficiency. Although a deficiency of any of several vitamins and minerals can produce anemia, only the most common—iron, vitamin B12, and folic acid—will be discussed here. Iron deficiency anemia is characterized as microcytic anemia because the RBCs become very small, while folic acid and B12 deficiency anemias are classified as macrocytic anemias because the RBCs become quite large.

Iron Deficiency Anemia

Iron is critical to human life. It plays the central role in the hemoglobin molecule of our red blood cells, where it transports oxygen from the lungs to the body’s tissues and carbon dioxide from the tissues to the lungs. Iron also functions in several key enzymes in energy production and metabolism including DNA synthesis.

Iron deficiency is the most common nutrient deficiency in the United States and the most common cause of anemia. The groups at highest risk for iron deficiency are infants under two years of age, teenage girls, pregnant women, and the elderly. Studies have found evidence of iron deficiency in as many as 30 to 50% of people in these groups. For example, some degree of iron deficiency occurs in 35 to 58% of young, healthy women. During pregnancy, the number is even higher. However, it must be pointed out that anemia is the last stage of iron deficiency. Iron-dependent enzymes involved in energy production and metabolism are the first to be affected by low iron levels. Serum ferritin is the best laboratory test for determining body iron stores.1

Iron deficiency may be caused by an increased iron requirement, decreased dietary intake, diminished iron absorption or utilization, blood loss, or a combination of factors. Increased requirements for iron occur during the growth spurts of infancy and adolescence and during pregnancy and lactation. Currently, the vast majority of pregnant women are routinely given iron supplements during their pregnancy, as the dramatically increased need for iron during pregnancy cannot usually be met through diet alone. Inadequate intake of iron is common in many parts of the world, especially areas where people consume a primarily vegetarian diet.

Typical infant diets in developed countries are high in milk and cereals and thus are also low in iron. The adolescent who eats a lot of junk food is at high risk for iron deficiency. However, those at greatest risk for a diet deficient in iron are the low-income elderly. This situation is complicated by the fact that decreased absorption of iron is very frequently found in the elderly. Decreased absorption of iron is often caused by a lack of hydrochloric acid secretion in the stomach, an extremely common condition in the elderly.

Other causes of decreased absorption include chronic diarrhea or malabsorption, the surgical removal of the stomach, and use of antacids or acid-blocking drugs. Blood loss is the most common cause of iron deficiency in women of childbearing age. This blood loss is most often due to excessive menstrual bleeding. Interestingly enough, iron deficiency is a common cause of excessive menstrual blood loss.2,3Other frequently seen causes of blood loss include bleeding from peptic ulcers, bleeding from hemorrhoids, and donating blood.

The negative effects of iron deficiency are due largely to the impaired delivery of oxygen to the tissues and the impaired activity of iron-containing enzymes in various tissues. Iron deficiency can lead to anemia, excessive menstrual blood loss, learning disabilities, impaired immune function, and decreased energy levels and physical performance.1

It has been clearly demonstrated that even a slight iron deficiency leads to a reduction in physical work capacity and productivity. The iron-dependent enzymes involved in energy production and metabolism will be impaired long before anemia occurs.1 Supplementation with iron has produced rapid improvements in work capacity among iron-deficient individuals.

Vitamin B12 Deficiency Anemia

Vitamin B12 deficiency is most often due to a defect in absorption, not a dietary lack. In order for vitamin B12 to be absorbed from food, it must be liberated from food by hydrochloric acid and bound to a substance known as intrinsic factor within the small intestine. Intrinsic factor is secreted by the parietal cells of the stomach. These same cells are responsible for the secretion of hydrochloric acid. Hence the secretion of intrinsic factor parallels that of hydrochloric acid. The B12–intrinsic factor complex is absorbed in the small intestine with the aid of the pancreatic enzyme trypsin.

In order for vitamin B12 to be absorbed, an individual must secrete enough hydrochloric acid, intrinsic factor, and pancreatic enzymes, including trypsin, and have a healthy and intact ileum (the end portion of the small intestine, where the vitamin B12–intrinsic factor complex is absorbed).

Lack of intrinsic factor results in a condition known as pernicious anemia. The defect is rare before the age of 35, and it is more common in individuals of Scandinavian, English, and Irish descent. It is much less common in southern Europeans, Asians, and blacks. Pernicious anemia is frequently associated with iron deficiency as well.

A dietary lack of vitamin B12 is most often associated with a vegan diet (a vegetarian diet that includes no milk products or eggs). Unlike other water-soluble nutrients, vitamin B12 is stored in the liver, kidney, and other body tissues. As a result, signs and symptoms of vitamin B12 deficiency may not show themselves until after five to six years of poor dietary intake or inadequate secretion of intrinsic factor. The classic symptom of vitamin B12 deficiency is pernicious anemia. However, it appears that a deficiency of vitamin B12 will affect the brain and nervous system before anemia develops.

The diagnosis of vitamin B12 deficiency is best made by measuring the vitamin B12 level in the blood. Most physicians, however, simply rely on the presence of large red blood cells and characteristic symptoms. Symptoms of severe B12 deficiency can include paleness; easy fatigability; shortness of breath; a sore, beefy red, and swollen tongue; diarrhea; and heart and nervous system disturbances.

The nervous system disturbances of a vitamin B12 deficiency can be quite serious. Common symptoms include numbness and tingling of the arms or legs, depression, mental confusion, loss of the ability to sense vibration, and loss of deep tendon reflexes. In the elderly, a vitamin B12 deficiency can mimic Alzheimer’s disease.

Folic Acid Deficiency

Folic acid deficiency is the most common vitamin deficiency in the world. The body does not store a large surplus of folic acid (unlike vitamin B12); it stores only enough to sustain itself for one to two months. Folic acid deficiency will result in the same type of anemia as that caused by a vitamin B12 deficiency: an anemia characterized by enlarged RBCs (macrocytic anemia). Other symptoms of folic acid deficiency include diarrhea, depression, and a swollen, red tongue.

Folic acid deficiency is extremely common among alcoholics, as alcohol consumption impairs absorption of folic acid, disrupts its metabolism, and causes the body to excrete it.

Folic acid deficiency is also common among pregnant women because of the developing fetus’s high demands. Folic acid is vital to cell reproduction within the fetus. If the fetus does not have a constant source of folic acid, birth defects such as neural tube defects may result. If alcohol is consumed during pregnancy, the alcohol may lower folic acid levels, leading to fetal alcohol syndrome or neural tube defects.

In addition to alcohol, there are a number of drugs that can induce folic acid deficiency, including anticancer drugs, drugs for epilepsy, and oral contraceptives.

Folic acid deficiency is quite common among patients who have chronic diarrhea or malabsorption states such as celiac disease, Crohn’s disease, or tropical sprue. Since a deficiency of folic acid will result in diarrhea and malabsorption, often a vicious circle ensues. The administration of folic acid as a preventive measure is warranted for anyone experiencing chronic diarrhea. Often this has a therapeutic effect as well.

The most sensitive test to assess folic acid deficiency is determining the folic acid content of the serum and RBC.

Therapeutic Considerations

The treatment of anemia is dependent on proper clinical evaluation by a physician. It is imperative that a comprehensive laboratory analysis of the blood be performed. Do not be satisfied with the diagnosis of “anemia.” It is critical that the underlying cause of the anemia be uncovered so that the correct therapy can be employed.

General Nutritional Support for All Types of Anemia

Perhaps the best food for an individual with any kind of anemia is calf liver. It is rich not only in iron but also in all B vitamins. Green leafy vegetables are also of great benefit to individuals with any kind of anemia. These vegetables contain natural fat-soluble chlorophyll (a molecule similar to the hemoglobin molecule) as well as other important nutrients, including iron and folic acid. Only fat-soluble chlorophyll can be absorbed from the gastrointestinal tract; the water-soluble form cannot and so has no use in the treatment of anemia.

Since a large percentage of individuals with anemia do not secrete enough hydrochloric acid, it is often important to take hydrochloric acid supplements with meals. See the chapter “Digestion and Elimination” for more information and dosage instructions.

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NOTE: It is always necessary to supplement vitamin B12 with folic acid to prevent the folic acid supplement from masking a vitamin B12 deficiency. Supplementing with folic acid will correct the anemia of a vitamin B12 deficiency, but it cannot overcome the problems that vitamin B12 deficiency causes in the brain. Also, a high level of folic acid will actually aggravate the problems caused by vitamin B12 deficiency.

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Support for Iron Deficiency Anemia

Again, treatment of any type of anemia should focus on underlying causes. For iron deficiency anemia, this typically involves finding a reason for chronic blood loss or for why an individual is not absorbing sufficient amounts of dietary iron. Lack of hydrochloric acid is a common reason for impaired iron absorption, especially among the elderly.

Increasing iron intake through food may partially or completely overcome poor iron absorption. There are two forms of dietary iron: heme iron and non-heme iron. Heme iron, found only in animal foods such as meat, poultry, and fish, is bound to the oxygen-binding proteins hemoglobin and myoglobin. It is the most efficiently absorbed form of iron. The absorption rate of non-heme iron, which is the kind found in plant food and in supplements such as ferrous sulfate and ferrous fumarate, is 2.9% on an empty stomach and 0.9% with food, much less than the absorption rate of heme iron, which is as high as 35%. In addition, heme iron is without the side effects associated with non-heme sources of iron, such as nausea, flatulence, constipation, and diarrhea.4

Despite the superiority of heme iron, nonheme iron salts are the most popular iron supplements. One reason is that even though heme iron is better absorbed, it is easy to take higher quantities of non-heme iron salts, so the net amount of iron absorbed is about equal. In other words, if you take 3 mg heme iron and 50 mg non-heme iron, the net absorption for each will be about the same.

Ferrous sulfate is the most popular iron supplement, but it is certainly less than ideal, as it often causes constipation or other gastrointestinal disturbances. The best forms of non-heme iron are ferrous succinate, glycinate, fumarate, and pyrophosphate. Of these, we prefer ferrous pyrophosphate that is micronized (made into a very small particle size) and then microencapsulated. The advantages of this form include that it is extremely stable, has no taste or flavor, is free from gastrointestinal side effects, and provides a sustained-release form of iron (up to 12 hours) with a high relative bioavailability, especially if it is taken on an empty stomach.5

For iron deficiency, the usual recommendation for any non-heme source is generally up to 60 mg per day in divided doses. High intakes of other minerals, particularly calcium, magnesium, and zinc, can interfere with iron absorption, so in treating iron deficiency it is recommended to take iron away from other mineral supplements. In contrast, vitamin C enhances iron absorption.

The best dietary sources of iron are red meat, especially liver. Good nonmeat sources of iron include fish, beans, molasses, dried fruits, whole grain and enriched breads, and green leafy vegetables.

The table below provides the iron content per serving of some of the better sources of iron. The table does not factor in absorption. For example, the absorption rate for the iron in calf liver is nearly 30%, while the absorption rate for the iron in vegetable sources is approximately 5%.

Dietary Sources of Iron

FOOD

AVERAGE SERVING SIZE (G)

IRON PER SERVING (MG)

Calf or lamb liver

60

9.6

Beef or chicken liver

60

5.2

Beef

90

2.7

Beans, cooked

100

2.3

Prunes

100

1.8

Bread (3 slices)

70

1.7

Chicken or turkey

90

1.6

Greens, cooked

75

1.5

Peas

75

1.5

Eggs

50

1.1

Several foods and beverages contain substances that inhibit iron absorption, including tea, coffee, wheat bran, and egg yolk. Antacids and overuse of calcium supplements also decrease iron absorption. These items should be restricted by individuals who have iron deficiency.1

Recommended Dietary Intakes (RDI) for Iron

GROUP

DAILY DOSE(MG)

Infants (7 months) up to age 10

10

Males 11–18 years old

12

Males 19 years and older

8

Females 11 years and older

18

Pregnant women

27

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Cautions and Warnings: Keep all iron supplements out of the reach of children. Acute iron poisoning in infants can result in serious consequences: damage to the intestinal lining, liver failure, nausea and vomiting, and shock.

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Support for Vitamin B12 Deficiency Anemia

In 1926, it was shown that injectable liver extracts were effective in the treatment of pernicious anemia. Soon after, active concentrates of liver became available for intramuscular as well as oral administration. Today, the use of liver and liver extracts has fallen out of favor in mainstream medicine. For pernicious anemia, standard medical treatment involves injecting vitamin B12 at a dose of 1,000 mcg per day for one week, but oral therapy has shown equal effectiveness (discussed in the section “Oral Versus Injectable B12,” below).

Vitamin B12 is found in significant quantities only in animal foods. The richest sources are liver and kidney, followed by eggs, fish, cheese, and meat. Vegans are often told that fermented foods such as tempeh and miso are excellent sources of vitamin B12. However, in addition to tremendous variation of B12 content in fermented foods, there is some evidence that the form of B12 in these foods is not the form that meets the human body’s requirements and is therefore useless. The same holds true for certain cooked sea vegetables. Although the vitamin B12 content of these foods is in the same range as beef, it is not known how well this form is utilized. Therefore, at this time we recommend that vegetarians, and particularly vegans, supplement their diets with vitamin B12.

Vitamin B12 is available in several forms. The most common form is cyanocobalamin. However, vitamin B12 is active in only two forms: methylcobalamin and adenosylcobalamin. Methylcobalamin is the only active form of vitamin B12 that is available commercially in tablet form in the United States. While methylcobalamin is active immediately upon absorption, cyanocobalamin must be converted by the body to either methylcobalamin or adenosylcobalamin. Cyanocobalamin is not active in many experimental models, while both methylcobalamin and adenosylcobalamin demonstrate exceptional activity.

Oral vs. Injectable B12

Although it is popular to inject vitamin B12, injection is not necessary; the oral administration of an appropriate dosage, even in the absence of intrinsic factor, can result in effective elevations of vitamin B12levels in the blood. This fact has gone relatively ignored among most physicians. In the United States, oral vitamin B12 therapy is rarely used despite the fact that it has been shown to be fully (100%) effective in the long-term treatment of pernicious anemia.6

Almost as soon as vitamin B12 was isolated in 1948, it was introduced in an injectable form, and researchers busily sought an oral alternative. Oral preparations containing intrinsic factor were tried, but some patients developed antibodies against intrinsic factor and therefore would not respond. Studies in the 1950s and 1960s soon documented that a small but constant proportion of an oral dose of cyanocobalamin was absorbed even without intrinsic factor through the process of diffusion, so by sufficiently increasing the dose, adequate absorption could be attained. A study in 1978 described 64 Swedish patients with pernicious anemia and other vitamin B12 deficiency states who were treated with 1,000 mcg of oral cyanocobalamin per day.7 Complete normalization of serum levels and liver stores for vitamin B12, as well as full clinical remission, was observed in all patients studied over a three-year period. Since that time numerous other studies have all confirmed the effectiveness of oral therapy with vitamin B12 for pernicious anemia.6

Despite the research, oral vitamin B12 therapy is still not used in the United States. Why? The short answer is education and bias. Physicians have erroneously been educated by medical texts that state that oral vitamin B12 therapy for pernicious anemia is “unpredictable,” has poor patient compliance, and is more costly. These same texts then state that oral cobalamin is effective and can be used when injection therapy is problematic, but the bias against oral treatment has already been established. In a survey of internists, 91% erroneously believed that vitamin B12 could not be absorbed in sufficient quantities without intrinsic factor. Interestingly, 88% of these doctors also stated that an effective oral vitamin B12 therapy would be useful in their practice and further added that it would be their preferred method of delivery if it was effective. Let’s reassure these doctors by answering the concerns regarding oral therapy.

• Is oral vitamin B12 therapy unpredictable? No, not at an effective dosage. Some of the early studies with oral B12 therapy used only 100 to 250 mcg per day. These reports led the U.S. Pharmacopoeia Anti-Anemia Preparations Advisory Board in 1959 to caution against oral therapy for pernicious anemia as being, “at best, unpredictably effective.” However, based on what is now known about oral vitamin B12absorption, the response to these low doses must now be considered predictable. It has been established that the average absorption rate of oral cyanocobalamin by patients with pernicious anemia is 1.2% across a wide range of dosages. Thus an oral dosage of 100 to 250 mcg per day results in a average absorption of 1.2 to 3 mcg, respectively—a dosage that is sufficient for many, but not all, patients. The bottom line is that higher dosages are necessary in order for most patients to benefit from oral therapy.

• How high must the dosage be to produce predictable improvements? The first month the dosage should be 2,000 mcg per day. After that a dosage of 1,000 mcg per day is recommended.

• Does oral vitamin B12 lead to poor patient compliance? No. The concern about patient compliance cited by the medical texts is irrational. Why is vitamin B12 singled out from all other oral therapies? It simply does not make any sense, especially since studies with oral cobalamin have shown excellent compliance. In many cases, the compliance is higher with an oral preparation, since many patients prefer taking a pill over getting a shot.

• Does oral vitamin B12 cost more than injectable? No way! The facts are that the two forms—injectable and oral—do not differ much in price for the vitamin B12 itself. The difference is in the cost charged to administer the vitamin B12 injection—anywhere from $20 in a private practice to $100 in a nursing home. As a result, the injectable form is considerably more expensive.

It should be obvious that there is no basis for the dogmatic belief that vitamin B12 must be administered by injection in order to produce clinical benefit. In the treatment of pernicious anemia, the usual dosage recommended by most medical texts is 1,000 mcg weekly for eight weeks, then once a month for life. For oral vitamin B12, the recommended dosage is 2,000 mcg per day (14,000 mcg weekly) for at least one month, followed by a daily intake of 1,000 mcg. Methylcobalamin, the active form of B12, is preferred over cyanocobalamin.

Support for Folic Acid Deficiency Anemia

The diet should focus on foods high in folic acid: liver, asparagus, dried beans, brewer’s yeast, dark green leafy vegetables, and whole grains. Since folic acid is destroyed by heat and light, fruits and vegetables should be eaten fresh or with very little cooking. Poor sources of folic acid include most meats, milk, eggs, and root vegetables.

To replenish folic acid stores, 800–1,000 mcg of folic acid should be taken every day for up to one month. Folic acid is available as folic acid (folate) and folinic acid (5-methyltetrahydrofolate). In order to utilize folic acid, the body must first convert it to tetrahydrofolate and then add a methyl group to form 5-methyltetrahydrofolate (folinic acid). Therefore, supplying the body with 5-methyltetrahydrofolate bypasses these steps and is needed for those with a genetic inability to make the conversion. Folinic acid is the most active form of folic acid and has been shown to be more efficient at raising body stores than folic acid.8

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QUICK REVIEW

• Identifying the cause of anemia through a complete diagnostic workup by a qualified health care professional is essential.

• Anemia caused by deficient red blood cell (RBC) production is almost always due to nutrient deficiency. The three most common forms are due to deficiencies of either iron, vitamin B12, or folic acid.

• Iron deficiency is the most common cause of anemia.

• Perhaps the best food for an individual with any kind of anemia is calf liver.

• Although it is popular to inject vitamin B12 in the treatment of vitamin B12 deficiency, injection is not necessary, as oral administration of an appropriate dosage has been shown to produce excellent results.

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TREATMENT SUMMARY

Effective therapy for anemia is dependent on proper diagnosis of its cause. The following recommendations are given with this in mind. Blood tests should be performed monthly to determine effective treatment.

Diet

The ingestion of 4 to 6 oz calf liver three to five times per week is recommended until the anemia is resolved, along with the liberal consumption of green leafy vegetables. Otherwise, follow the recommendations given in the chapter “A Health-Promoting Diet.”

Nutritional Supplements

In addition to the recommendations given in the chapter “Supplementary Measures,” here are specific recommendations for each type of anemia.

• For iron deficiency anemia:

  images Iron: 30 mg, bound to either pyrophosphate, succinate, glycinate, or fumarate, twice per day between meals (if this recommendation results in abdominal discomfort, take 30 mg with meals three times per day)

  images Vitamin C: 1 g three times per day with meals

• For vitamin B12 deficiency anemia:

  images Oral vitamin B12: 2,000 mcg per day for at least one month, followed by 1,000 mcg per day (methylcobalamin, the active form of vitamin B12, supplied in sublingual tablets, is preferable to cyanocobalamin)

  images Folic acid: 800 to 1,200 mcg three times per day

• For folic acid deficiency anemia:

  images Folic acid: 800 to 1,200 mcg three times per day

  images Vitamin B12: 1,000 mcg per day (it is always necessary to supplement vitamin B12 with folic acid to prevent the folic acid supplement from masking a vitamin B12 deficiency)